2,127
Views
1
CrossRef citations to date
0
Altmetric
Hematology

Cytopenias following anti-CD19 chimeric antigen receptor (CAR) T cell therapy: a systematic analysis for contributing factors

ORCID Icon, , , ORCID Icon, , & ORCID Icon show all
Pages 2950-2964 | Received 05 Jul 2022, Accepted 11 Oct 2022, Published online: 16 Nov 2022

References

  • Haslauer T, Greil R, Zaborsky N, et al. CAR T-cell therapy in hematological malignancies. Int J Mol Sci. 2021;22(16):8996.
  • Schubert ML, Schmitt M, Wang L, et al. Side-effect management of chimeric antigen receptor (CAR) T-cell therapy. Ann Oncol. 2021;32(1):34–48.
  • Nagle SJ, Murphree C, Raess PW, et al. Prolonged hematologic toxicity following treatment with chimeric antigen receptor T cells in patients with hematologic malignancies. Am J Hematol. 2021;96(4):455–461.
  • Fried S, Avigdor A, Bielorai B, et al. Early and late hematologic toxicity following CD19 CAR-T cells. Bone Marrow Transplant. 2019;54(10):1643–1650.
  • Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20(1):31–42.
  • Logue JM, Zucchetti E, Bachmeier CA, et al. Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma. Haematologica. 2021;106(4):978–986.
  • Bethge WA, Martus P, Schmitt M, et al. GLA/DRST real-world outcome analysis of CAR-T cell therapies for large B-cell lymphoma in Germany. Blood. 2022;140(4):349–358.
  • Larson RC, Maus MV. Recent advances and discoveries in the mechanisms and functions of CAR T cells. Nat Rev Cancer. 2021;21(3):145–161.
  • Schaefer A, Huang Y, Kittai A, et al. Cytopenias after CD19 chimeric antigen receptor T-Cells (CAR-T) therapy for diffuse large B-Cell lymphomas or transformed follicular lymphoma: a single institution experience. Cancer Manag Res. 2021;13:8901–8906.
  • Slim K, Nini E, Forestier D, et al. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg. 2003;73(9):712–716.
  • Gill SI, Frey NV, Hexner E, et al. Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia. Blood Adv. 2022;online ahead of print:2022007317.
  • Geyer MB, Rivière I, Sénéchal B, et al. Autologous CD19-targeted CAR T cells in patients with residual CLL following initial purine analog-based therapy. Mol Ther. 2018;26(8):1896–1905.
  • Neelapu SS, Dickinson M, Munoz J, et al. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nat Med. 2022;28(4):735–742.
  • Locke FL, Miklos DB, Jacobson CA, All ZUMA-7 Investigators and Contributing Kite Members, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640–654.
  • Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–2544.
  • Jacobson CA, Chavez JC, Sehgal AR, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022;23(1):91–103.
  • Shah NN, Johnson BD, Schneider D, et al. Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial. Nat Med. 2020;26(10):1569–1575.
  • Spiegel JY, Patel S, Muffly L, et al. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med. 2021;27(8):1419–1431.
  • Cordoba S, Onuoha S, Thomas S, et al. CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Nat Med. 2021;27(10):1797–1805.
  • Ortíz-Maldonado V, Rives S, Castellà M, et al. CART19-BE-01: a multicenter trial of ARI-0001 cell therapy in patients with CD19+ relapsed/refractory malignancies. Mol Ther. 2021;29(2):636–644.
  • Liu R, Cheng Q, Kang L, et al. CD19 or CD20 CAR T cell therapy demonstrates durable antitumor efficacy in patients with central nervous system lymphoma. Hum Gene Ther. 2022;33(5-6):318–329.
  • Wei G, Zhang Y, Zhao H, et al. CD19/CD22 dual-targeted car t-cell therapy for relapsed/refractory aggressive b-cell lymphoma: a safety and efficacy study. Cancer Immunol Res. 2021;9(9):1061–1070.
  • Schuster SJ, Svoboda J, Chong EA, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017;377(26):2545–2554.
  • Yan ZX, Li L, Wang W, et al. Clinical efficacy and tumor microenvironment influence in a dose-escalation study of anti-CD19 chimeric antigen receptor T cells in refractory B-cell non-Hodgkin’s lymphoma. Clin Cancer Res. 2019;25(23):6995–7003.
  • Sesques P, Ferrant E, Safar V, et al. Commercial anti-CD19 CAR T cell therapy for patients with relapsed/refractory aggressive B cell lymphoma in a European center. Am J Hematol. 2020;95(11):1324–1333.
  • Hu Y, Zhou Y, Zhang M, et al. CRISPR/Cas9-engineered universal CD19/CD22 dual-targeted CAR-T cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia. Clin Cancer Res. 2021;27(10):2764–2772.
  • Roddie C, Dias J, O'reilly MA, et al. Durable responses and low toxicity after fast off-rate cd19 chimeric antigen receptor-t therapy in adults with relapsed or refractory b-cell acute lymphoblastic leukemia. J Clin Oncol. 2021;39(30):3352–3363.
  • Wang N, Hu X, Cao W, et al. Efficacy and safety of CAR19/22 T-cell cocktail therapy in patients with refractory/relapsed B-cell malignancies. Blood. 2020;135(1):17–27.
  • Gu R, Liu F, Zou D, et al. Efficacy and safety of CD19 CAR T constructed with a new anti-CD19 chimeric antigen receptor in relapsed or refractory acute lymphoblastic leukemia. J Hematol Oncol. 2020;13(1):122.
  • Ghorashian S, Kramer AM, Onuoha S, et al. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat Med. 2019;25(9):1408–1414.
  • Zhang H, Liu M, Li Q, et al. Evaluation of the safety and efficacy of humanized anti-CD19 chimeric antigen receptor T-cell therapy in older patients with relapsed/refractory diffuse large B-cell lymphoma based on the comprehensive geriatric assessment system. Leuk Lymphoma. 2022;63(2):353–361.
  • Myers RM, Li Y, Leahy AB, et al. Humanized CD19-Targeted chimeric antigen receptor (CAR) T cells in CAR-Naive and CAR-Exposed children and young adults with relapsed or refractory acute lymphoblastic leukemia. J Clin Oncol. 2021;39(27):3044–3055.
  • Baird JH, Epstein DJ, Tamaresis JS, et al. Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma. Blood Adv. 2021;5(1):143–155.
  • Gauthier J, Gazeau N, Hirayama AV, et al. Impact of CD19 CAR T-cell product type on outcomes in relapsed or refractory aggressive B-NHL. Blood. 2022;139(26):3722–3731.
  • Cheng Z, Wei R, Ma Q, et al. In vivo expansion and antitumor activity of coinfused CD28- and 4-1BB-engineered CAR-T cells in patients with B cell leukemia. Mol Ther. 2018;26(4):976–985.
  • Ramos CA, Rouce R, Robertson CS, et al. In vivo fate and activity of second- versus third-generation CD19-specific CAR-T cells in B cell non-Hodgkin’s lymphomas. Mol Ther. 2018;26(12):2727–2737.
  • Wudhikarn K, Palomba ML, Pennisi M, et al. Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma. Blood Cancer J. 2020;10(8):79.
  • Lyu C, Cui R, Wang J, et al. Intensive debulking chemotherapy improves the short-term and long-term efficacy of anti-CD19-CAR-T in refractory/relapsed DLBCL with high tumor bulk. Front Oncol. 2021;11:706087.
  • Wang Y, Li H, Song X, et al. Kinetics of immune reconstitution after anti-CD19 chimeric antigen receptor T cell therapy in relapsed or refractory acute lymphoblastic leukemia patients. Int J Lab Hematol. 2021;43(2):250–258.
  • Shah BD, Bishop MR, Oluwole OO, et al. KTE-X19 anti-CD19 CAR T-cell therapy in adult relapsed/refractory acute lymphoblastic leukemia: ZUMA-3 phase 1 results. Blood. 2021;138(1):11–22.
  • Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell therapy in relapsed or refractory Mantle-Cell lymphoma. N Engl J Med. 2020;382(14):1331–1342.
  • Shah BD, Ghobadi A, Oluwole OO, et al. KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study. The Lancet. 2021;398(10299):491–502.
  • Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet (London, England. 2020;396(10254):839–852.
  • Zhang Y, Wang Y, Liu Y, et al. Long-term activity of tandem CD19/CD20 CAR therapy in refractory/relapsed B-cell lymphoma: a single-arm, phase 1–2 tria. Leukemia. 2022;36(1):189–196.
  • Wang Y, Cao J, Gu W, et al. Long-term follow-up of combination of B-cell maturation antigen and CD19 chimeric antigen receptor T cells in multiple myeloma. J Clin Oncol. 2022;40(20):2246–2256.
  • Frey NV, Gill S, Hexner EO, et al. Long-Term outcomes from a randomized dose optimization study of chimeric antigen receptor modified T cells in relapsed chronic lymphocytic leukemia. J Clin Oncol. 2020;38(25):2862–2871.
  • Kochenderfer JN, Somerville RPT, Lu T, et al. Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum interleukin-15 levels. J Clin Oncol. 2017;35(16):1803–1813.
  • Maschan M, Caimi PF, Reese-Koc J, et al. Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients. Nat Commun. 2021;12(1):7200.
  • Liu X, Zhang Y, Li K, et al. A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. Transl Oncol. 2021;14(7):101085.
  • Sun M, Xu P, Wang E, et al. Novel two-chain structure utilizing KIRS2/DAP12 domain improves the safety and efficacy of CAR-T cells in adults with r/r B-ALL. Mol Ther Oncolytics. 2021;23:96–106.
  • Ying Z, He T, Wang X, et al. Parallel comparison of 4-1BB or CD28 Co-stimulated CD19-targeted CAR-T cells for B cell non-Hodgkin’s lymphoma. Mol Ther Oncol. 2019;15:60–68.
  • Locke FL, Neelapu SS, Bartlett NL, et al. Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017;25(1):285–295.
  • Siddiqi T, Soumerai JD, Dorritie KA, et al. Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL. Blood. 2022;139(12):1794–1806.
  • Kato K, Makita S, Goto H, et al. Phase 2 study of axicabtagene ciloleucel in japanese patients with relapsed or refractory large B-cell lymphoma. Int J Clin Oncol. 2022;27(1):213–223.
  • Chen X, Li X, Liu Y, et al. A phase i clinical trial of chimeric antigen receptor-modified T cells in patients with relapsed and refractory lymphoma. Immunotherapy. 2020;12(10):681–696.
  • Fan L, Wang L, Cao L, et al. Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients. Front Med. 2022;16(2):285–294.
  • Zhou X, Tu S, Wang C, et al. Phase I trial of Fourth-Generation anti-CD19 chimeric antigen receptor T cells against relapsed or refractory B cell Non-Hodgkin lymphomas. Front Immunol. 2020;11:564099.
  • Enblad G, Karlsson H, Gammelgård G, et al. A phase I/IIa trial using CD19-targeted third-generation CAR T cells for lymphoma and leukemia. Clin Cancer Res. 2018;24(24):6185–6194.
  • Sang W, Shi M, Yang J, et al. Phase II trial of co-administration of CD19- and CD20-targeted chimeric antigen receptor T cells for relapsed and refractory diffuse large B cell lymphoma. Cancer Med. 2020;9(16):5827–5838.
  • Hu Y, Wu Z, Luo Y, et al. Potent anti-leukemia activities of chimeric antigen receptor-modified T cells against CD19 in chinese patients with relapsed/refractory acute lymphocytic leukemia. Clin Cancer Res. 2017;23(13):3297–3306.
  • Talleur A, Qudiemat A, Métais JY, et al. Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. Blood Adv. 2022; online ahead of print:2021006293.
  • Zhang Y, Li J, Lou X, et al. A prospective investigation of bispecific CD19/22 CAR T cell therapy in patients with relapsed or refractory B cell Non-Hodgkin lymphoma. Front Oncol. 2021;11:664421.
  • Sim AJ, Jain MD, Figura NB, et al. Radiation therapy as a bridging strategy for CAR T cell therapy with axicabtagene ciloleucel in diffuse large B-cell lymphoma. Int J Radiat Oncol Biol Phys. 2019;105(5):1012–1021.
  • Ying Z, Yang H, Guo Y, et al. Relmacabtagene autoleucel (relma-cel) CD19 CAR-T therapy for adults with heavily pretreated relapsed/refractory large B-cell lymphoma in China. Cancer Med. 2021;10(3):999–1011.
  • Kadauke S, Myers RM, Li Y, et al. Risk-adapted preemptive tocilizumab to prevent severe cytokine release syndrome after CTL019 for pediatric B-Cell acute lymphoblastic leukemia: a prospective clinical trial. J Clin Oncol. 2021;39(8):920–930.
  • Ying Z, Huang XF, Xiang X, et al. A safe and potent anti-CD19 CAR T cell therapy. Nat Med. 2019;25(6):947–953.
  • Brudno JN, Lam N, Vanasse D, et al. Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Nat Med. 2020;26(2):270–280.
  • Geyer MB, Rivière I, Sénéchal B, et al. Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed/refractory CLL. JCI Insight. 2019;5(9):e122627.
  • Bishop MR, Dickinson M, Purtill D, et al. Second-Line tisagenlecleucel or standard care in aggressive B-cell lymphoma. N Engl J Med. 2022;386(7):629–639.
  • Pan J, Zuo S, Deng B, et al. Sequential CD19-22 CAR T therapy induces sustained remission in children with r/r B-ALL. Blood. 2020;135(5):387–391.
  • Heng G, Jia J, Li S, et al. Sustained therapeutic efficacy of humanized anti-CD19 chimeric antigen receptor T cells in relapsed/refractory acute lymphoblastic leukemia. Clin Cancer Res. 2020;26(7):1606–1615.
  • Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet (London, England). 2015;385(9967):517–528.
  • Fowler NH, Dickinson M, Dreyling M, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med. 2022;28(2):325–332.
  • Curran KJ, Margossian SP, Kernan NA, et al. Toxicity and response after CD19-specific CAR T-cell therapy in pediatric/young adult relapsed/refractory B-ALL. Blood. 2019;134(26):2361–2368.
  • Brudno JN, Somerville RPT, Shi V, et al. Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. J Clin Oncol. 2016;34(10):1112–1121.
  • Schuster SJ, Bishop MR, Tam CS, JULIET Investigators, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45–56.
  • Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439–448.
  • Yamashita M, Iwama A. Aging and clonal behavior of hematopoietic stem cells. Int J Mol Sci. 2022;23(4):1948.
  • Huttunen R, Heikkinen T, Syrjanen J. Smoking and the outcome of infection. J Intern Med. 2011;269(3):258–269.
  • Shah NN, Fry TJ. Mechanisms of resistance to CAR T cell therapy. Nat Rev Clin Oncol. 2019;16(6):372–385.
  • Shah NN, Maatman T, Hari P, et al. Multi targeted CAR-T cell therapies for B-Cell malignancies. Front Oncol. 2019;9:146.
  • Luo W, Li C, Zhang Y, et al. Adverse effects in hematologic malignancies treated with chimeric antigen receptor (CAR) T cell therapy: a systematic review and meta-analysis. BMC Cancer. 2022;22(1):98.
  • Amini L, Silbert SK, Maude SL, et al. Preparing for CAR T cell therapy: patient selection, bridging therapies and lymphodepletion. Nat Rev Clin Oncol. 2022;19(5):342–355.
  • Nastoupil LJ, Jain MD, Feng L, et al. Standard-of-care axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma: results from the US lymphoma CAR T consortium [J]. J Clin Oncol. 2020;38(27):3119–3128.
  • Pinnix CC, Gunther JR, Dabaja BS, et al. Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma. Blood Adv. 2020;4(13):2871–2883.
  • Huang R, Li X, He Y, et al. Recent advances in CAR-T cell engineering. J Hematol Oncol. 2020;13(1):86.
  • Jain T, Knezevic A, Pennisi M, et al. Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies. Blood Adv. 2020;4(15):3776–3787.
  • Wagner DL, Fritsche E, Pulsipher MA, et al. Immunogenicity of CAR T cells in cancer therapy. Nat Rev Clin Oncol. 2021;18(6):379–393.
  • Labbe RP, Vessillier S, Rafiq QA. Lentiviral vectors for T cell engineering: clinical applications, bioprocessing and future perspectives. Viruses. 2021;13(8):1528.
  • Turtle CJ, Hanafi LA, Berger C, et al. Immunotherapy of non-Hodgkin’s lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med. 2016;8(355):355ra116.